Itch is a common and sometimes disabling clinical problem. Several lines of evidence indicate that spinothalamic tract (STT) neurons in primates carry pruriceptive information. Our recent search for pruriceptive (itch coding) STT primate neurons projecting to the ventral posterior lateral nucleus (VPL) of thalamus suggest that these account only for the nociceptive qualities evoked by pruritic stimuli. But further studies are needed to complete our survey of these neurons. A major goal of this project is to examine the responses to pruritic stimuli of neurons that form several of the other major components of the STT in primates. We will use mechanical, thermal and chemical pmritic stimuli including histamine and cowhage spicules -the latter believed to evoke a histamine-independent itch - that are used in psychophysical studies of itch in Project 1. We will identify STT neurons that project to either VPL or to the ventral posterior inferior or posterior nuclei of thalamus using micro-antidromic stimulation methods. We will determine the responses of these neurons to pruritic stimuli and statistically match the responses to psychophysical functions that describe the latency, intensity and duration of itch or pain produced by these and other stimuli. This will allow us to determine whether an examined neuron responds specifically or selectively to pruritic or nociceptive stimuli. Pruritic chemicals produce large areas of itchy skin (alloknesis). We will determine whether changes in the responses of STT neurons can account for occurrence of itchy skin. We will also determine whether the potentially important class of very slowly conducting STT axons that have been described in cats also exist in monkeys and if they respond to pruritic and nociceptive stimuli. In the final series of experiments, we will examine the effects of cutaneous manipulations that are known to increase or decrease the sensation of itch (including warming, cooling, and scratching) on pruritic responses of STT neurons. These studies should provide insight into to the mechanisms in both the spinal cord and thalamus underlying itch and its inhibition, and, thereby, potentially lead to improved treatments of chronic itch.